Causal effects of potential risk factors on postpartum depression: a Mendelian randomization study

Mingrong Zuo; Zhihao Wang; Wenhao Li; Siliang Chen; Yunbo Yuan; Yuan Yang; Qing Mao; Yanhui Liu

doi:10.3389/fpsyt.2023.1275834

Causal effects of potential risk factors on postpartum depression: a Mendelian randomization study

Front Psychiatry. 2023 Dec 20:14:1275834. doi: 10.3389/fpsyt.2023.1275834. eCollection 2023.

Authors

Mingrong Zuo^#¹, Zhihao Wang^#¹, Wenhao Li¹, Siliang Chen¹, Yunbo Yuan¹, Yuan Yang¹, Qing Mao¹, Yanhui Liu¹

Affiliation

¹ Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, China.

^# Contributed equally.

Abstract

Background: Postpartum depression (PPD) is a type of depressive episode related to parents after childbirth, which causes a variety of symptoms not only for parents but also affects the development of children. The causal relationship between potential risk factors and PPD remains comprehensively elucidated.

Methods: Linkage disequilibrium score regression (LDSC) analysis was conducted to screen the heritability of each instrumental variant (IV) and to calculate the genetic correlations between effective causal factors and PPD. To search for the causal effect of multiple potential risk factors on the incidence of PPD, random effects of the inverse variance weighted (IVW) method were applied. Sensitivity analyses, including weighted median, MR-Egger regression, Cochrane's Q test, and MR Pleiotropy Residual Sum and Outlier (MR-PRESSO), were performed to detect potential Mendelian randomization (MR) assumption violations. Multivariable MR (MVMR) was conducted to control potential multicollinearity.

Results: A total of 40 potential risk factors were investigated in this study. LDSC regression analysis reported a significant genetic correlation of potential traits with PPD. MR analysis showed that higher body mass index (BMI) (Benjamini and Hochberg (BH) corrected p = 0.05), major depression (MD) (BH corrected p = 5.04E-19), and schizophrenia (SCZ) (BH corrected p = 1.64E-05) were associated with the increased risk of PPD, whereas increased age at first birth (BH corrected p = 2.11E-04), older age at first sexual intercourse (BH corrected p = 3.02E-15), increased average total household income before tax (BH corrected p = 4.57E-02), and increased years of schooling (BH corrected p = 1.47E-11) led to a decreased probability of PPD. MVMR analysis suggested that MD (p = 3.25E-08) and older age at first birth (p = 8.18E-04) were still associated with an increased risk of PPD.

Conclusion: In our MR study, we found multiple risk factors, including MD and younger age at first birth, to be deleterious causal risk factors for PPD.

Keywords: Mendelian randomization; causal factors; linkage disequilibrium score regression; mental disorder; postpartum depression.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by the Sichuan Science and Technology Program (2023YFQ0002 to YL) and the Sichuan Science and Technology Program (2023YFG0127 to YuaY).